The acid-base constant of an anaesthetic drug, propofol, was determined in different acetonitrile-water mixtures by using multiwavelength spectrophotometric titration data. The pH values measured in acetonitrile-water mixtures with a glass electrode calibrated with an aqueous buffer, s w pH, were corrected to obtain s s pH, that is, the pH of the acetonitrile-water mixture as measured with a glass electrode calibrated with a buffer in the same solvent mixture. This last pH scale is directly related to the thermodynamic acid-base constant. The pKa value of propofol in pure water was found to be 11.67. Linear relationships were observed when the calculated pKa values of propofol in different solvent mixtures were plotted against the acetonitrile molar fraction. Also, a linear relationship was observed between pKa values and the reciprocal of the relative permittivity of the solvent mixture, 1/epsilon. This behavior was taken as indicative of the electrostatic nature of the ionization process.
propofol; spectrophotometric titrations; acidity constant; solvent mixtures
